Preprint Article Version 2 Preserved in Portico This version is not peer-reviewed

Performance of a 7-Type HPV mRNA Test in Triage of HPV DNA Primary Screen Positive Women Compared to Liquid-Based Cytology

Version 1 : Received: 6 January 2023 / Approved: 10 January 2023 / Online: 10 January 2023 (07:13:00 CET)
Version 2 : Received: 25 February 2023 / Approved: 28 February 2023 / Online: 28 February 2023 (01:50:35 CET)

A peer-reviewed article of this Preprint also exists.

Sørbye, S.W.; Falang, B.M.; Antonsen, M. Performance of a 7-Type HPV mRNA Test in Triage of HPV DNA Primary Screen Positive Women Compared to Liquid-Based Cytology. J. Mol. Pathol. 2023, 4, 69-80. Sørbye, S.W.; Falang, B.M.; Antonsen, M. Performance of a 7-Type HPV mRNA Test in Triage of HPV DNA Primary Screen Positive Women Compared to Liquid-Based Cytology. J. Mol. Pathol. 2023, 4, 69-80.

Abstract

Background: A plethora of data supports HPV-based screening to be the preferred strategy for cervical cancer prevention. The shift to a more sensitive firstline test brings the need of effective triage up for discussion. Currently, most algorithms apply cytology as triage of HPV-DNA positive women. This study compared the performance of a 7-type HPV-mRNA test to cytology. Methods: From 2019-01-01, until 2021-12-31, cervical samples from 58,029 women were examined at the University Hospital of North Norway. 30.5% (17,684/58,029) fulfilled the criteria for HPV-DNA primary screening. All positive samples were triaged by cytology and followed-up according to national guidelines through 2022. Additionally, a 7-type HPV-mRNA test was applied. Study endpoint was histologically confirmed high grade lesion (CIN2+). Results: 5.6% (990/17,684) had positive HPV-DNA test, 97.2% (962/990) with valid HPV-mRNA results. 55.5% (534/962) had abnormal cytology (ASC-US+) and 35.1% (338/962) had positive HPV-mRNA test. 13.9% (134/962) had CIN2+. Sensitivity (CIN2+) of cytology versus the HPV-mRNA test was 76.1% (102/134)) versus 73.1% (98/134)), p=0.67. The specificity was 47.8% (396/828) versus 71.0% (588/624), p<0.001. PPV was 19.1% (102/534) and 29.0% (98/338), p<0.001 respectively. The number of colposcopies per CIN2+ detected by cytology and HPV-mRNA test was 5.2 and 3.1. Conclusion: The 7-type HPV mRNA test was significant more specific than cervical cytology in triage of HPV-DNA positive women. Using this biomarker as threshold for colposcopy may better balance the benefits and harms of screening.

Keywords

HPV-DNA; primary screening; HPV-mRNA; biomarker; triage; liquid-based cytology; colposcopy; CIN2+

Subject

Medicine and Pharmacology, Pathology and Pathobiology

Comments (1)

Comment 1
Received: 28 February 2023
Commenter: Sveinung Sorbye
Commenter's Conflict of Interests: Author
Comment: All women participating in HPV primary screening in North Norway (Troms and Finnmark county) over the period 2019-01-01 throughout 2021-12-31 (17,684) have been followed up according to the Norwegian guidelines, resulting in a CIN2+ prevalence among study population at 9.8% (94/962).The study is ongoing, and we have revised the manuscript to include the results for women followed up throughout December 2022, increasing the number of CIN2+ cases from (n=94) to (n=134) being eligible for re-analysis, hereby allowing for a more accurate comparison between the two triage methods.
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